Atrial Fibrillation and Sudden Death in HF K Shivkumar MD
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Transcript of Atrial Fibrillation and Sudden Death in HF K Shivkumar MD
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Kalyanam Shivkumar, MD, PhDDirector, UCLA Cardiac Arrhythmia Center & EP Program
Division of Cardiology, Department of MedicineDavid Geffen School of Medicine at UCLA
Los Angeles, California
Kalyanam Shivkumar, MD, PhDDirector, UCLA Cardiac Arrhythmia Center & EP Program
Division of Cardiology, Department of MedicineDavid Geffen School of Medicine at UCLA
Los Angeles, California
Atrial Fibrillation andSudden Death in
Heart Failure
Atrial Fibrillation andSudden Death in
Heart Failure
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Atrial Fibrillation in Heart Failure
• Background
• Pathophysiology
• Influence on disease state and progression
• Clinical approach
• Management
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Atrial Fibrillation in HF: Background
• Heart failure and atrial fibrillation are ‘emerging epidemics’
• Tachycardia mediated cardiomyopathyin 10% patients
• Prevalence of atrial fibrillation increases with worsening ventricular dysfunction
• Atrial fibrillation may increase mortality
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Correlation Between AF and HF Severity:
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Atrial Fibrillation in Heart Failure
• Background
• Pathophysiology
• Influence on disease state and progression
• Clinical approach
• Management
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Atrial Fibrillation in Heart Failure: Pathophysiology
• Structural changes such as fibrosis are prominent in remodeled atria in the setting of heart failure
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Myocardial Fibrosis: Structural Remodeling in Atrial Fibrillation
Li D et al. Circulation. Jul 1999;100:87-95.
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Atrial Fibrillation in HF:Functional Changes
ICaL and ‘window’
Ito
Ik1 If
Tra
nsm
emb
ran
e P
ote
nti
al(M
illi
volt
s)
-50
0
50
-100 Threshold
INa
Ikr, Ikur,
Iksus
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Atrial Fibrillation in HF: Pathophysiology
• Reductions in L-type Ca2+ current, apparently caused by transcriptional
downregulation of the 1c pore-forming Ca2+-channel subunit, Cav1.2, are
important in mediating electrophysiological changes caused by atrial tachycardia remodeling
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Shiroshita-Takeshita, Schram, Lavoie, and Nattel. Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs. Circulation. 2004;110:2313-2319.
Effect of Simvastatin and Antioxidant Vitamins on Atrial FibrillationDue to Remodeling: L-type Ca Channel Alpha Subunit Protein
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Pathophysiology of AtrialFibrillation in Heart Failure
• Coupling• Liminal length changes secondary
to stretch• Changes in coupling/geometry of
the atrial muscle bundles at the pulmonary vein-atrial junction
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• Atrial Stretch– Stretch activated channels– Anionic currents
• Modulation by autonomic influences
• Neurohumoral changes
Pathophysiology of AtrialFibrillation in Heart Failure
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Stretch-Related Changes in Conduction of Electrical Impulses from the Pulmonary Veins into the Atria in an Animal Model of Atrial Fibrillation
Kalifa et al. Circulation. 2003;108:668.
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Stretch-Related Changes in Frequency of Excitation of the Pulmonary Veins and Atria in an Animal Model of Atrial Fibrillation
Kalifa et al. Circulation. 2003;108:668.
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Asirvatham and Friedman.
From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF. 2005.
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Integration of Clinical andExperimental Data
AF (short duration)
AF (variable duration)
DISEASED ATRIUM + Trigger (?Accentuation of preexisting heterogeneity)
NORMAL ATRIUM + Trigger (preexisting heterogeneity)
REMODELINGPERMANENTAtrial Fibrillation
Shivkumar K and Weiss JN. Atrial fibrillation from cells to computers. Cardiovasc Res. 2001.
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Atrial Fibrillationin Heart Failure
• Background
• Pathophysiology
• Influence on disease state and progression
• Clinical approach
• Management
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Pozolli et al. 1998;31(1):197-204.
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The DIG Investigators. Chest. 2000;118:914-922.
From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF.
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SOLVD Investigators: J Am Coll Cardiol. 1998;32:695-703.
From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF.
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Atrial Fibrillationin Heart Failure
• Background
• Pathophysiology
• Influence on disease state and progression
• Clinical approach
• Management
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Atrial Fibrillation in Heart Failure:Clinical Approach
• Assure guideline-based medical management
• Assess structural issues (dilatation due to valve regurgitation, diastolic dysfunction, etc)
• Anticoagulation
• Rhythm management
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Management of Atrial Fibrillation in Heart Failure
• Pharmacological– Heart Failure therapy– Antiarrhythmic drugs
• Non Pharmacological– Catheter ablation (atria)– AV nodal ablation and bi-V pacing– Atrial defibrillators
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Anne W, Willems R, Van der Merwe N, et al. AF after RF ablation of atrial flutter: preventive effect of ACEI, ARB and diuretics. Heart. 2004;90:1025-1030.
Pharmacological Management: Effect of Heart Failure Drugs
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Pharmacological Management: Effect of Heart Failure Drugs
Anne W, Willems R, Van der Merwe N, et al. AF after RF ablation of atrial flutter: preventive effect of ACEI, ARB and diuretics. Heart. 2004;90:1025-1030.
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Antiarrhythmic Drugs: Efficacy MaintainingNSR ≥6 Months
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CTAF TrialCTAF Trial
N Engl J Med. 2000;342:913-920.
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J Am Coll Cardiol. 2003;42:20-29.
AFFIRM : Antiarrhythmic Drug SubstudyAFFIRM : Antiarrhythmic Drug Substudy
(P<0.01)
(n=106)
(n=125)
(n=116)
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Diamond Study: Overall Survival
Myocardial Infarction Congestive Heart Failure
Torp-Pedersen C et al. N Engl J Med. 1999;341:857-865.
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Odds Ratio for Total Mortality for PatientsOdds Ratio for Total Mortality for PatientsTreated with Quinidine Compared to ControlTreated with Quinidine Compared to Control
Coplen SE. Circulation. 1990;82:1106-1116.
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Catheter Ablation of Atrial Fibrillation: How to Ablate
• Surgical Maze
• Pulmonary vein isolation
• Left atrial catheter ablation
• Mapping and ablating complex potentials
• Mapping and ablation fat pads
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Initiation of ‘Focal’ Atrial FibrillationRSPV
RIPVLSPV
LIPV
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Cabrera et al. Circulation. 2002;106:968.
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Evolving Strategy for Ablation of ‘Focal’ Atrial Fibrillation
ABLATION OF FOCUS
ELECTRICAL ISOLATION
UCLA Cardiac Arrhythmia Center.
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Who to Ablate?
• Symptomatic drug-refractoryatrial fibrillation
• Drug intolerance
• Tachycardia-induced cardiomyopathy
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Catheter Ablation FocalAtrial Fibrillation: Results
• Maintenance of sinus rhythm without drugs
• Drug control of previously drug-refractory atrial fibrillation
• Failure to have any impact on the arrhythmia
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• 60-80%
Catheter Ablation FocalAtrial Fibrillation: Results
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Safety Issues
• Pulmonary Vein Stenosis• Cerebrovascular accident (CVA)• Bezold-Jarisch response (?RSPV)• Phrenic nerve injury (RSPV)• Cardiac tamponade• Pulmonary parenchymal hemorrhage and
bronchial vein damage• Atrioesophageal fistula formation
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Permanent Atrial Fibrillation
• Catheter ‘maze’
• Cryo-‘maze’
• ?Epicardial cryogenic application
• Atrial anti-tachycardia devices
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Ozcan et al. N Eng J Med. 2001;344:1043-1051.
From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF.
Long-Term Survival After Ablation of the AV Node and Implantationof a Permanent Pacemaker
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Role of Implanted Devices
• Sick Sinus Syndrome
• Anti-tachy pacing
• Preventive algorithms (eg, DAO)
• Cardioversion
• Dual site pacing
• Monitoring capabilities
• Palliative (vent rate stabilization)
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Sudden Death in HF
• Background
• Pathophysiology
• Clinical Management
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Ischemic Ventricular Arrhythmiasin the USA
Acute Myocardial Infarction: (per year)
Myocardial infarctions: 1,500,000
Pre hospital deaths: 300,000 (>95% VT/VF)
In hospital deaths: 120,000 (20% VT/VF)
Post hospital deaths: 80,000 (10-50% VT/VF)
Stevenson et al. Cardiac arrhythmias, where to go from here?In: Brugada P, Wellens HJJ; eds. Futura Publishing Co; 1987:377-389.
Zipes and Wellens. Circulation. 1998;21:2334-2351.
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Scope of the Problem
• 0.75-1 million ‘new’ CHF cases a year
• 50% of patients die suddenly
• Improved survival of patients ‘unmasks’ other causes of morbidity and mortality
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Scope of the Problem
• Every infarct survivor is a potential congestive heart failure patient who will need CHF and sudden cardiac death risk reduction
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Sudden Death in HF
• Background
• Pathophysiology
• Clinical Management
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Alterations of Gross Structure: Remodeling
Reentrant circuit
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Bello, Kipper, Valderrabano, and Shivkumar. Heart Rhythm. 2004.
Structure-Function-Metabolism Correlation
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Alterations in Myocardial Microarchitecture
• Loss of myocytes
• Changes in cell-cell communication
• Discontinuous electrical propagation
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Sudden Death in HF
• Background
• Pathophysiology
• Clinical Management
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Antiarrhythmic Drugs or Conventional Therapy vs ICDs
VT/VF PatientsAVIDCASHCIDS
Post-MI Patients MADITCABG Patch
CABG PatchSCD-HeFTMADIT 2
Heart Failure Patients
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Moss et al. N Engl J Med. 2002.
Primary Prevention: MADIT-II
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SCD-HeFTMortality by Intention to Treat
30 60544842360 6 12 18 24
0.1
0.2
0.3
0.4
0
Mo
rtal
ity
HR 97.5%CI P Value
Amiodarone vs Placebo 1.06 0.86, 1.30 0.529ICD Therapy vs Placebo 0.77 0.62, 0.96 0.007
Amiodarone Placebo
ICD Therapy
Months of follow-upMonths of follow-up
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60
70
80
90
100
0 60 120 180 240 300 360
Days in Trial
Cum
ulat
ive
Sur
viva
l (%
)
QRS QRS Duration Duration (msec)(msec)
<90<90
90-12090-120
120-170120-170
170-220170-220
>220>220
Wide QRS:Proportional Mortality Increase
• NYHA Class II-IV patients• 3,654 ECGs digitally scanned• Age, creatinine, LVEF,
heart rate, and QRS duration found to be independent predictors of mortality
• Relative risk of widest QRS group 5x greater than narrowest
11 Gottipaty V, Krelis S, Lu F, et al. Gottipaty V, Krelis S, Lu F, et al. J Am Coll Cardiol.J Am Coll Cardiol. 1999;33(2):145 [Abstr847-4]. 1999;33(2):145 [Abstr847-4].
Vesnarinone StudyVesnarinone Study11
(VEST study analysis)(VEST study analysis)
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CRT Trials
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• The most effective anti-heart failure intervention is a statin
• The most effective anti-sudden death intervention is also a statin
• Perhaps the most effective anti-atrial fibrillation drug may very well be a statin!
Conclusion